aaha-selected-endocrinopathies-of-dogs-and-cats-guidelines

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2023 AAHA Selected Endocrinopathies of Dogs
and Cats Guidelines
Andrew Bugbee, DVM, DACVIM,† Renee Rucinsky, DVM, DABVP (Feline Practice),† Sarah Cazabon, DVM,
Heather Kvitko-White, DVM, DACVIM, Patty Lathan, VMD, MS, DACVIM (Small Animal Internal Medicine),
Amy Nichelason, DVM, DABVP (Canine and Feline), Liza Rudolph, BAS, RVT, VTS (Canine and Feline)
(Small Animal Internal Medicine)
ABSTRACT
Canine and feline endocrinopathies reflect an endocrine gland disease or dysfunction with resulting hormonal abnormali-
ties that can variably affect the patient’s wellbeing, quality of life, and life expectancy. These guidelines provide consensus
recommendations for diagnosis and treatment of four canine and feline endocrinopathies commonly encountered in clini-
cal practice: canine hypothyroidism, canine hypercortisolism (Cushing’s syndrome), canine hypoadrenocorticism (Addi-
son’s disease), and feline hyperthyroidism. To aid the general practitioner in navigating these common diseases, a
stepwise diagnosis and treatment algorithm and relevant background information is provided for managing each of these
diseases. The guidelines also describe, in lesser detail, the diagnosis and treatment of three relatively less common endo-
crinopathies of cats: feline hyperaldosteronism, feline hypothyroidism, and feline hyperadrenocorticism. Additionally, the
guidelines present tips on effective veterinary team utilization and client communication when discussing endocrine
cases. (J Am Anim Hosp Assoc 2023; 59:�–�. DOI 10.5326/JAAHA-MS-7368)
AFFILIATIONS
Department of Small Animal Medicine and Surgery, University of Georgia,
Athens, Georgia (A.B.); Mid Atlantic Cat Hospital, Mid Atlantic Feline Thyroid
Center, Queenstown, Maryland (R.R.); Boston Veterinary Clinic, Boston,
Massachusetts (S.C.); KW Veterinary Consulting, LLC, Kansas City, Missouri
(H.K.-W.); Mississippi State University, Mississippi State, Mississippi (P.L.);
School of Veterinary Medicine, University of Wisconsin-Madison, Madison,
Wisconsin (A.N.); Rowan College of South Jersey, Sewell, New Jersey (L.R.)
CONTRIBUTING REVIEWERS
Audrey Cook, BVM&S, FRCVS, DACVIM-SAIM, DECVIM-CA, DABVP
(Feline), Texas A&M University Department of Small Animal Clinical Sciences
Daniel Langlois, DVM, DACVIM, Michigan State University College of Veteri-
nary Medicine
Correspondence: abugbee@uga.edu (A.B.); rucinsky.mach@gmail.com (R.R.)
† A. Bugbee and R. Rucinsky are the cochairs of the AAHA Selected
Endocrinopathies of Dogs and Cats Guidelines Task Force.
These guidelines were prepared by a task force of experts convened by
the American Animal Hospital Association. This document is intended as
a guideline only, not an AAHA standard of care. These guidelines and
recommendations should not be construed as dictating an exclusive pro-
tocol, course of treatment, or procedure. Variations in practice may be
warranted based on the needs of the individual patient, resources, and
limitations unique to each individual practice setting. Evidence-guided
support for specific recommendations has been cited whenever possible
and appropriate. Other recommendations are based on practical clinical
experience and a consensus of expert opinion. Further research is
needed to document some of these recommendations. Drug approvals
and labeling are current at the time of writing but may change over time.
Because each case is different, veterinarians must base their decisions
on the best available scientific evidence in conjunction with their own
knowledge and experience.
The 2023 AAHA Selected Endocrinopathies of Dogs and Cats Guide-
lines are generously supported by Boehringer Ingelheim Animal Health,
IDEXX, Merck, Zoetis, and Zomedica.
ACTH (adrenocorticotropic hormone); ACTHST (adrenocorticotropic hor-
mone stimulation test); ADH (adrenal-dependent hyperadrenocortisolism);
ALP (alkaline phosphatase); ALT (alanine aminotransferase); CKD (chronic
kidney disease); CS (Cushing’s syndrome); DOCP (desoxycorticosterone
pivalate); FHT (feline hyperthyroidism); fT4 (free thyroxine); fT4ed (free thyrox-
ine by equilibrium dialysis); HA (hypoadrenocorticism); HAC (hyperadreno-
corticism); 131I (radioactive iodine); LDDST (low-dose dexamethasone
suppression test); PDH (pituitary-dependent hyperadrenocortisolism); PHA
(primary hyperaldosteronism); SHT (systemic hypertension); T3 (triiodothyro-
nine); T4 (thyroxine); TSH (thyroid-stimulating hormone); TT4 (total thyroxine
concentration); UCCR (urine cortisol-to-creatinine ratio)
© 2023 by American Animal Hospital Association JAAHA.ORG 1
VETERINARY PRACTICE GUIDELINES
https://doi.org/10.5326/JAAHA-MS-7368
mailto:abugbee@uga.edu
mailto:rucinsky.mach@gmail.com
Introduction
Veterinary clinicians routinely encounter and are expected to manage
various endocrinopathies in their canine and feline patients. Most
commonly, these conditions include canine hypothyroidism, canine
hypercortisolism (Cushing’s syndrome), canine hypoadrenocorticism
(Addison’s disease), and feline hyperthyroidism (FHT). Canine and
feline diabetes mellitus is not discussed in these guidelines but is
addressed in previously published guidelines.1 These endocrinopathies
can be overt or have minimal clinical impact, especially in early-stage
disease. Diagnosis relies on a recognition of clinical signs or physical
examination abnormalities, careful compilation of the patient’s his-
tory, interpretation of hormone concentration assays, and exclusion
of comorbidities that can complicate an accurate diagnosis. Early
intervention in endocrinopathy cases avoids the severe syndromes
that can impact the patient’s quality of life and cause secondary organ
damage and mortality. The guidelines are designed to provide practi-
tioners with a practical, stepwise approach to the diagnosis and treat-
ment of the four most common canine and feline endocrinopathies.
The guidelines introduce each endocrinopathy by providing a
definition and clinical profile of the disease. In addition to the four
principal diseases described in the guidelines, three less common
feline endocrinopathies are also discussed: feline hyperaldosteronism,
feline hypothyroidism, and feline hyperadrenocorticism. The guide-
lines are not intended to cover all endocrinopathies that affect dogs
and cats, but to provide a foundation for accurate recognition and
diagnosis and effective clinical management of the most common
endocrine-related morbidities. Practitioners will benefit from con-
sulting the abundant literature to gain additional clinical perspectives
on each disease.
The guidelines discuss the four principal endocrinopathies
using an innovative, categorical approach to diagnosis based on clin-
ical presentation, as previously described in the 2016 AAFP Guide-
lines for the Management of Feline Hyperthyroidism.2 This approach
evaluates the patient’s clinical presentation as determined by the
attending veterinarian, combined with the patient’s medical history
as reported by the client. The clinical presentation of each disease is
summarized in a table, which also includes the next steps for diag-
nosis and treatment. Accompanying the table is a more detailed,
referenced narrative specific to each disease. The table is a prescrip-
tive, quick-reference tool, whereas the narrative provides useful con-
textual background for making informed clinical decisions.
The most successful veterinary practices recognize the impor-
tance of engaging the owner in the management of a pet’s health.
The dialog with the client should involve the entire practice
team. Accordingly, these guidelines also include a section on practice
team and client considerations. When all those involved in the
patient’s wellbeing are well informed and engaged, better adherence
to treatment recommendations and improved case outcomes is
expected.
Canine Hypothyroidism
Overview
Hypothyroidism is most commonly an acquired condition of adult
dogs characterized by primaryazotemia, etc.
Goiter present, equivocal 
dermatologic signs: 
consider TSH testing
Is this cat older than 2 years and symptomatic?
maybe
FHT, feline hyperthyroidism; T4, thyroxine; 
TSH, thyroid-stimulating hormone level.
FIGURE 1
Decision Tree for Feline Hypothyroidism Diagnosis and Treatment.
TABLE 11
Clinical Signs of Feline Hypothyroidism
Congenital Disease
• Slow growth rate
• Short limbs
• Broad head
• Lethargy
• Constipation
• Mental dullness
• Retained deciduous teeth
• Gingival overgrowth
• Retained kitten hair coat
Iatrogenic or Adult-Onset Disease
• Lethargy 
• Weight gain, obesity
• Seborrhea, poor haircoat
• Poor regrowth of hair
• Inappetence
• Bradycardia
18 JAAHA | 59:3 May/Jun 2023
extremely uncommon problem. Treatment should only be consid-
ered for cats with repeatable laboratory abnormalities and clinical
signs consistent with hypothyroidism, such as lethargy, poor hair
coat, and obesity. Confirmation of decreased serum T4 on more
than one occasion, along with elevated TSH levels, is required to
establish the diagnosis.
Iatrogenic hypothyroidism is caused by overdosing with antithy-
roid drugs such as methimazole, surgical removal of the thyroid
glands, or 131I treatment. Once patients have been stabilized on
methimazole, monitoring at least every 6 mo will ensure proper thy-
roid control and avoidance of hypothyroidism. When treating with
131I, consideration should be given to the T4 and TSH levels and the
131I should be dosed appropriately.82 Failing to recognize and address
iatrogenic hypothyroidism can contribute to decreased renal func-
tion.83 Maintaining T4 levels between 1.0 and 2.5 mcg/dL is ideal, and
treatment should be initiated for patients with T4 values ,1.0mcg/dL
and an elevated TSH level. Additionally, cats with T4 levels within the
reference range but an elevated TSH who develop a new or progres-
sive azotemia may benefit from methimazole dose reduction or
levothyroxine supplementation if surgically or 131I treated.
Feline Hyperadrenocorticism/Hypercortisolism
Hyperadrenocorticism (HAC), also referred to as hypercortisolism
or Cushing’s syndrome, is an infrequent diagnosis of cats. Similar to
dogs, cats usually have pituitary-dependent HAC, and the hormonal
mechanism of action is the same as in dogs. Clinical signs are due to
the excess circulating glucocorticoid levels. Cats seem to be rarely
negatively affected by chronic use of exogenous glucocorticoids, so
the incidence of iatrogenic Cushing’s syndrome in cats is much less
frequent compared with dogs.84
HAC usually affects middle-aged to older cats, with the majority
having concurrent diabetes mellitus that may be considered difficult
to regulate. It is important to note that most difficult diabetic cases
do not have HAC, and other causes of poor diabetic regulation
should be pursued first. Clinical signs of HAC in cats are often non-
specific and include weakness, abdominal distension, and dermato-
logical issues such as fragile skin and failure to regrow hair. Cats
with concurrent diabetes mellitus are usually polyuric, polydipsic,
and polyphagic, but these signs reflect persistent hyperglycemia
rather than CS per se. Weight loss, lethargy, and gastrointestinal
signs are possible but uncommon.
A minimum database will most commonly show hyperglycemia
and glucosuria. Changes that are common in canine HAC are not as
predictable in feline patients. Alkaline phosphatase levels are usually
normal in cats who lack the steroid-induced isoenzyme, and hyper-
cholesterolemia may be present. A stress leukogram is present in
only half of feline cases. Definitive diagnosis in cats may be challeng-
ing, with the most reliable diagnosis coming from the LDDST. It is
important to note that dexamethasone dosing for cats is greater than
the effective canine dose. Cats must be dosed at 0.1 mg/kg dexameth-
asone IV.82 The interpretative criteria are similar to those used in
dogs, with a lack of suppression at 4 or 8 hr after administration con-
firming the diagnosis of HAC. UCCR testing may also be used for
initial screening. At least two morning samples should be collected at
home by the owner and submitted for evaluation.85 A positive result
from UCCR testing should be followed up with an LDDST, but a
negative result likely rules out the diagnosis of HAC. An ACTH
stimulation test is not recommended as a diagnostic tool in cats
because of its poor sensitivity to detect feline HAC compared with
the other available testing.85
Differentiation testing to determine if the HAC is caused by a
pituitary tumor or adrenal tumor can be considered, as adrenalect-
omy may be curative in cats with unilateral adrenal tumors. Radia-
tion therapy may be beneficial in cats with PDH.
Medical treatment with trilostane is the mainstay of HAC treat-
ment in cats, with a recommended dosing of �1 mg/kg given two to
three times daily with food.83 The licensed product may be reformulated
if doses significantly less than 5 mg per dose are needed. The goal of
treatment for feline HAC is control of clinical signs, and strict monitor-
ing of cortisol levels may not be critical for treatment success. Improve-
ment of weight, polyuria/polydipsia, polyphagia, and overall quality of
life are the primary treatment goals. Laboratory monitoring with CBC,
biochemical profiles, and urinalysis 7–14 days after starting trilostane
and every 3–4 mo thereafter is recommended. If cortisol monitoring is
pursued, the UCCR testing and ACTH stimulation test have been most
commonly used to ensure trilostane is not leading to hypocortisolism.
Final decisions on dosing, however, should be based on clinical assess-
ment of the cat by both the veterinarian and the owner, the status of any
concurrent disease, and the prevention of hypocortisolism.
Clinical Tips
• Poorly regulated diabetes in cats usually has an etiology
other than HAC.
• Compared with the canine dose for LDDST, a higher
dexamethasone dose is needed in cats: 0.1 mg/kg of
dexamethasone is consistently effective in suppressing
healthy cats but not cats with HAC.86
• Three-times-a-day dosing of trilostane may be needed
to reach therapeutic doses with standard capsule sizes.
• Reformulation of the licensed product may be required
for smaller doses.
2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines—Final
JAAHA.ORG 19
• Clinical evaluation of the cat and any concurrent dis-
eases may be more important than targeted monitoring
of adrenal function.
The Team Approach
From initial patient presentation to long-term management, the pet
owner interacts with every veterinary health care team member.
Embracing a team-based approach can help establish clients’ trust,
promote communication and compliance, and improve overall
patient care and quality of life.
Receptionists and client-service coordinators are often the first
interaction the pet owner will have with the veterinary practice.
Developing communication resources and telephone triage skills will
help the nonclinical staff determine appropriate scheduling for ill
patients and those requiring ongoing monitoring with timed testing
or even potentially life-threatening situations.
The patient history that is obtained by the credentialed veteri-
nary technician or veterinary assistant plays an essential role in veter-
inary case management for endocrinopathies. The patient history
focuses on the pet’s health from the point of view of the pet owner,
which is invaluable as this information cannot be wholly determined
by physical examination and diagnostic test results alone. An accu-
rate history is helpful in determining the duration and severity of
clinical signs, developing a problem list or prioritizing differentials,
and monitoring a patient’s response to therapeutic interventions. For
example, knowing the likelihood of toxin exposure may help the vet-
erinarian assess a patient in a hypoadrenocortical crisis, whenthe
possibility of an acute kidney injury may confound the diagnosis.
Communication tips on how to take a quality patient
history:
� Encourage the use of a pet owner questionnaire.
� Standardized history taking may promote continuity of care and
monitoring of trends.
� Templates can be tailored for different situations—wellness, sick vis-
its, ongoing monitoring for chronic diseases, etc.
� Address clients in a clear and courteous manner.
� Speak respectfully and avoid using medical jargon or slang.
� Start with open-ended questions.
� Establish the presenting complaint and pet owner’s concerns with
questions such as, “Can you describe to me what happened?” or
“What brings you in today?”
� Endeavor not to interrupt the pet owner, as valuable information
may be missed.
� After identifying the presenting complaint, progress to more focused
closed-ended questions to clarify the situation, such as, “How long
has this been happening?” or “How often does this occur?”
� Allow for pauses.
� Let the client gather their thoughts. Try not to rush them to fill the
silence.
� Practice positive nonverbal communication. Use open body pos-
tures, direct eye contact, and head nodding.
� Engage in reflective listening.
� After the client finishes talking, reflect on what was heard and
ask if the situation has been understood correctly. For example,
“Annabelle vomited five times since yesterday; is that correct?”
� Express empathy.
� When talking to pet owners, the veterinary health care team
should be able to understand the owner’s situation and be able to
communicate that to them. For example, “I know you care for
Simon, and I understand this can be overwhelming.”
In addition to acquiring a patient history from the owner
regarding the presenting complaint, one must also inquire about the
general status of the pet (including diet) and past pertinent medical
history and obtain an accurate medication history. When asking
about medications, one must be clear to specifically ask about pre-
ventives, over-the-counter medications, supplements or nutraceuti-
cals, and any topical medications. Owners often only think of oral
prescription medications and may not think to divulge important
information, such as the use of topical exogenous corticosteroid
products.
Clear communication with the pet owner and the veterinary
team facilitates ongoing care and monitoring. Without proper com-
munication and established protocols, scheduling something as sim-
ple as an ACTHST can be problematic if the owner, client-service
coordinator, credentialed veterinary technician, or veterinary assis-
tant does not know when an ACTHST should begin after trilostane
administration. Additionally, one must remember that dose adjust-
ments are not made in a diagnostic vacuum. Clinical signs and phys-
ical examination are equally important factors in successful ongoing
patient management.
As these patients visit the veterinary practice more frequently
for monitoring, prioritizing patient comfort and reducing stress will
go a long way in building the veterinary health care team’s relation-
ship with the pet and their owner. Not only will low-stress visits rein-
force pet owner compliance for timely follow-up, but they will also
encourage more reliable diagnostic results as stress can influence
many endocrine-related diagnostics. For example, using devices such
as butterfly catheters for ACTHST and LDDST to facilitate both
obtaining a baseline sample and administering the appropriate medi-
cation with a single venipuncture has the benefit of reducing stress
and minimizing discomfort and vessel trauma when compared with
repeated venipuncture events.
Another example of prioritizing patient comfort to support con-
sistent diagnostic values to monitor trends is blood pressure mea-
surement. The 2018 ACVIM Consensus Statement: Guidelines for the
20 JAAHA | 59:3 May/Jun 2023
Identification, Evaluation, and Management of Systemic Hypertension
in Dogs and Cats includes a helpful protocol for accurate blood pres-
sure measurement in small animal patients.87
Regardless of the endocrinopathy, the veterinary health care
team is instrumental in educating the pet owner. For successful man-
agement, the client should have a basic understanding of the disease,
the clinical signs, adverse events, long-term goals, and recommenda-
tions regarding treatment and ongoing care.
Conclusion
Canine and feline practitioners will inevitably encounter the endocri-
nopathies discussed in these guidelines. The clinical signs of these
diseases are typically nonspecific and often highly variable and in
some cases can be iatrogenic in origin. Early-stage disease can be
subclinical. Adding to the complexity of endocrine disease is the
possibility of comorbidities, some of which can be secondary to
advancing age, as in the case of canine hypothyroidism and hyper-
cortisolism and feline hyperthyroidism. Collectively, these factors
place a premium on diagnostic testing and an accurate patient his-
tory to arrive at a diagnosis and effective treatment plan. Careful
treatment monitoring is indicated in endocrinopathy management,
including noting the presence or resolution of clinical signs, trends
in endogenous hormone levels, and therapeutic dose adjustments.
The guidelines are intended to help practitioners logically decon-
struct the ambiguous presentations that often characterize endocrine
diseases. The algorithm tables included in the guidelines are designed
to enable practitioners to quickly work through a diagnostic and
treatment progression to address these often-challenging cases.
The authors declare no conflicts of interest.
The authors gratefully acknowledge the contribution of Mark
Dana of Kanara Consulting Group, LLC, in the preparation of
the manuscript and Robyn Jolly for her assistance during the
task force meeting.
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classic hypoadrenocorticism with glucocorticoid-deficient hypoadreno-
corticism in dogs: 46 cases (1985–2005). J Am Vet Med Assoc 2007;
230(8):1190–4.
48. Borin-Crivellenti S, Garabed RB, Moreno-Torres K I, et al. Use of a
combination of routine hematologic and biochemical test results in a
logistic regression model as a diagnostic aid for the diagnosis of hypoa-
drenocorticism in dogs. Am J Vet Res 2017;78(10):1171–81.
49. Wakayama JA, Furrow E, Merkel LK, et al. A retrospective study of dogs
with atypical hypoadrenocorticism: a diagnostic cut off or continuum?
J Small Anim Pract 2017;58(7):365–71.
50. Seth M, Drobatx KJ, Church DB, et al. White blood cell count and the
sodium to potassium ratio to screen for hypoadrenocorticism in dogs.
J Vet Intern Med 2011;25:1351–6.
51. Adler JA, Drobatz KJ, Hess RS. Abnormalities of serum electrolyte con-
centrations in dogs with hypoadrenocorticism. J Vet Intern Med 2007;21:
1168–73.
52. Baumstark ME, Sieber-Ruckstuhl NS, Muller C, et al. Evaluation of aldo-
sterone concentrations in dogs with hypoadrenocorticism. J Vet Intern
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53. Bovens C, Tennant K, Reeve J, Murphy KF. Basal serum cortisol concen-
tration as a screening test for hypoadrenocorticism in dogs. J Vet Intern
Med. 2014;28(5):1541–5.
54. Javadi S, Galc S, Boer P, et al. Aldosterone-renin and cortisol-to-
adrenocorticotropic hormone ratios in healthy dogs and dogs with pri-
mary hypoadrenocorticism. J Vet Intern Med 2006;20:556–61.
55. Lathan P, Scott-Moncrieff JC, and Wills RW. Use of the cortisol-to-
ACTH ratio for diagnosis of primary hypoadrenocorticism in dogs. J Vet
Intern Med 2014;28:1546–50.
56. Zycortal suspension (desoxycorticosterone pivalate injectable suspen-
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57. Moya MV, Refsal KR, Langlois DK. Investigation of the urine cortisol to
creatinine ratio for the diagnosis of hypoadrenocorticism in dogs. J Am
Vet Med Assoc 2022;260(9):1041–7.
58. Del Baldo F, Gerou Ferriani M, Bertazzolo W,Luciani M, Tardo AM,
Fracassi F. Urinary cortisol-creatinine ratio in dogs with hypoadrenocor-
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59. Bates JA, Shott S, Schall WD. Lower initial dose desoxycorticosterone
pivalate for treatment of canine primary hypoadrenocorticism. Aust Vet
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60. Kintzer PP, Peterson ME. Treatment and long-term follow-up of 205
dogs with hypoadrenocorticism. J Vet Intern Med 1997;11(2):43–9.
61. Sieber-Ruckstuhl NS, Reusch CE, Hofer-Inteeworn N, et al. Evaluation
of a low-dose desoxycorticosterone pivalate treatment protocol for long-
term management of dogs with primary hypoadrenocorticism. J Vet
Intern Med 2019;33(3):1266–71.
62. Vincent AM, Okonkowski LK, Brudvig JM, et al. Low-dose desoxycorti-
costerone pivalate treatment of hypoadrenocorticism in dogs: a random-
ized controlled clinical trial. J Vet Intern Med 2021;35(4):1720–8.
63. Botsford A, Behrend EN, Kemppainen RJ, et al. Low-dose ACTH stimu-
lation testing in dogs suspected of hypoadrenocorticism. J Vet Intern
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64. Frank LA, Oliver J. Comparison of serum cortisol concentrations in clin-
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65. Asirvatham JR, Moses V, Bjornson L. Errors in potassium measurement:
a laboratory perspective for the clinician. N Am J Med Sci 2013;5(4):
255–9.
66. Lathan P, Thompson AL. Management of hypoadrenocorticism (Addi-
son’s disease) in dogs. Vet Med (Auckl) 2018;9:1–10.
67. Hibbert A, Gruffydd-Jones T, Barrett EL, et al. Feline thyroid carcinoma:
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68. Peterson ME, Rishniw M. Predicting outcomes in hyperthyroid cats trea-
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75. Peterson ME. More than just T4. Diagnostic testing for hyperthyroidism
in cats. J Feline Med Surg 2013;15:765–77.
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77. Griffin S. Feline abdominal ultrasonography: what’s normal? what’s
abnormal? The adrenal glands. J Feline Med Surg 2021;23(1):33–49.
78. Kooistra HS. Primary hyperaldosteronism in cats: an underdiagnosed
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79. Daminet S. Feline hypothyroidism. In: Mooney CT, Peterson ME, eds.
Manual of Canine and Feline Endocrinology. 4th ed. Quedgeley, Glouces-
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primary hypothyroidism in 7 adult cats [published correction appears
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81. Peterson, ME, Carothers, MA, Gamble, DA, et al. Spontaneous primary
hypothyroidism in 7 adult cats. J Vet Intern Med 2018;32:1864–73.
82. Fernandez Y, Puig J, Powell R, et al. Prevalence of iatrogenic hypothy-
roidism in hyperthyroid cats treated with radioiodine using an indivi-
dualised scoring system. J Feline Med Surg 2019;21(12):1149–56.
83. Finch NC, Stallwood J, Tasker S, et al. Thyroid and renal function in
cats following low-dose radioiodine (111Mbq) therapy. J Small Anim
Pract 2019;60:523–8.
84. Boland LA, Barrs VR. Peculiarities of feline hyperadrenocorticism:
update on diagnosis and treatment. J Feline Med Surg 2017;19(9):933–47.
85. Feldman EC. Hyperadrenocorticism in cats. In: Feldman E, Nelson R,
Reusch C, et al., eds. Canine and Feline Endocrinology. 4th ed. St. Louis:
Elsevier; 2015:452–84.
86. Hoenig M. Feline hyperadrenocorticism–where are we now? J Feline
Med Surg 2002;4(3):171–4.
87. Acierno MJ, Brown S, Coleman AE, et al. ACVIM consensus statement:
guidelines for the identification, evaluation, and management of systemic
hypertension in dogs and cats. J Vet Intern Med 2018;32(6):1803–22.
2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines—Final
JAAHA.ORG 23failure of the thyroid gland to produce
adequate amounts of thyroxine (T4) and triiodothyronine (T3). Path-
ogenesis commonly involves immune-mediated destruction of func-
tional thyroid tissue (thyroiditis) or idiopathic thyroid atrophy, which
may represent end-stage thyroiditis.3 Well-documented breed associa-
tions support a genetic susceptibility, with a selection of commonly
affected breeds including English setters, Doberman pinschers, Rho-
desian ridgebacks, and golden and Labrador retrievers.4–7 Disruption
of other portions of the thyroid axis are rarely reported as causes of
hypothyroidism, such as reduced secretion of pituitary thyroid-
stimulating hormone (TSH) or hypothalamic thyrotropin-releasing
hormone.8 Congenital hypothyroidism resulting from inherited gen-
etic defects or abnormal thyroid gland development have been rarely
reported in dogs.9–11
Diagnostic Testing and Monitoring
Clinical signs of canine hypothyroidism often manifest in middle
age, with a mean age at diagnosis reported to be 6.8 yr.12 Signs may
be subtle and slowly progress over months to years. Dermatologic
abnormalities occur frequently and often include truncal nonpruritic
alopecia, “rat tail” appearance, poor coat quality, seborrhea, hyper-
pigmentation, and recurrent pyoderma.6 Other commonly reported
clinical signs include lethargy, mental dullness, exercise intolerance,
obesity or unexplained weight gain, and heat-seeking behaviors. Less
commonly reported associations include facial nerve paralysis, vestib-
ular disease, and polyneuropathy.13
Abnormalities on initial biochemical screening are nonspecific,
with a fasted hypercholesterolemia, hypertriglyceridemia, and mild
nonregenerative anemia most commonly found.14 Hypothyroid dogs
are expected to have a total thyroxine concentration (TT4) below the
laboratory reference range; a result in the upper half of the reference
range generally excludes the condition. If clinical suspicion of hypo-
thyroidism is high in a patient with a TT4 below or in the lower end
of the reference interval, evaluation of free T4 (fT4) and TSH con-
centrations is warranted. Although equilibrium dialysis is preferred
for fT4 testing (fT4ed), it is not essential, and assay availability
should be confirmed with the laboratory. Definitive hypothyroidism
diagnosis is characterized by TT4 and fT4 concentrations below the
reference interval with a TSH concentration above the reference
interval; however, �20–40% of dogs with overt hypothyroidism will
2 JAAHA | 59:3 May/Jun 2023
have TSH concentrations within the reference range.15,16 Therefore,
having two of the three hormone concentrations indicative of hypo-
thyroidism is enough to support the diagnosis in a patient with com-
patible clinical or biochemical abnormalities. An isolated TT4 below
the reference interval should not be the only criteria used to diagnose
hypothyroidism. Practitioners must consider that reduction of TT4
concentrations can occur secondary to patient breed, advancing age,
and administration of certain medications, such as prednisone, as
well as during periods of illness or stress.17,18 Severe illness can also
suppress fT4 concentrations, further mimicking a hypothyroid state;
therefore, thyroid testing should ideally be performed following clini-
cal stabilization or disease recovery when possible, to maximize the
diagnostic accuracy of results.19
Therapy
Treatment involves oral hormone replacement using levothyroxine
sodium at a starting dosage of 0.02 mg/kg twice daily. In obese
patients, dose calculations should be based on estimated lean body
weight. Veterinary approved medications should be used and given
on an empty stomach. If given with food, higher doses of supple-
mentation may be needed to overcome reductions in bioavailability
and dose monitoring should be performed in a nonfasted state so
results accurately reflect the patient’s response. Clinical signs typically
improve rapidly once therapy is started; however, dermatologic
abnormalities may be slower to resolve.
Treatment monitoring is initiated 4 wk after starting supplemen-
tation unless signs persist in the face of therapy or signs of iatrogenic
hyperthyroidism develop. Monitoring includes TT4 assessment, with
the blood sample obtained 4–6 hr after medication administration
(“post-pill”) to check the peak serum concentration. Dose adjustments
are performed as needed monthly until the post-pill serum TT4 con-
centration is in the upper half or slightly above the laboratory’s refer-
ence range, or within the range for dogs receiving supplementation if
provided by the laboratory. If an elevated TSH concentration was pre-
sent at diagnosis, it should return to the reference range following
treatment; however, confirming TSH normalization is not required
and adds additional cost to monitoring. Once control is achieved,
twice-daily dosing can be continued indefinitely with TT4 monitoring
performed every 6–12 mo. Alternatively, after several months of
twice-daily dosing, patients can possibly be transitioned to once-daily
medication administration. A serum sample is obtained at the time
the medication is due (“pre-pill”). A trough TT4 concentration
.1.5 mcg/dL suggests the dose is likely adequate for once-daily
administration. Pre-pill TT4 concentrations ,1.5 mcg/dL warrant
either continuation of twice-daily dosing or increasing the once-daily
dose by at least 50% and assessing a month later. Both pre- and
4–6 hr post-pill monitoring would be necessary at this visit to ensure
TABLE 1
Summary of Categorical Approach to Diagnosing Suspected Canine Hypothyroidism
2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines—Final
JAAHA.ORG 3
the dose increase avoids iatrogenic hyperthyroidism and provides suf-
ficient 24 hr hormone replacement.
Clinical Tips
• Certain breeds and active working dogs are known to
have thyroid hormone concentrations that are below
standard laboratory reference ranges in the absence of
thyroid disease. Therefore, it is essential to consider the
patient’s breed and purpose when presented with abnor-
mal thyroid hormone concentration results. This is
especially important in sighthounds, such as greyhounds
or salukis.20–22
• Although uncommon, circulating autoantibodies against
thyroxine (T4) can cross-react with the TT4 assay, caus-
ing an artificially high reported result. A free T4 by
equilibrium dialysis (fT4ed) or quantification of circu-
lating autoantibodies may be warranted any time a nor-
mal dog is found to have an elevated TT4 concentration
or in patients with clinical or biochemical abnormalities
suggesting hypothyroidism but a TT4 concentration
within reference range.5,23
Categorical Approach to Diagnosis Based on Clinical
Presentation
Hypothyroidism is one of the most common endocrinopathies of the
dog, and a clear-cut diagnosis can be made when the signalment and
presentation of symptoms are classic and are supported by appropri-
ate endocrine test results. However, the guidelines authors acknowl-
edge that hypothyroidism is commonly overdiagnosed owing to the
nonspecific nature of the signs, as well as the challenges that arise
with the interpretation of thyroid function testing.
GROUP 1: DOGS WITH CLASSICAL SIGNS OF
HYPOTHYROIDISM AND A LOW TT4
Clinical Presentation
� Signalment: middle-aged dogs and breed predisposition (beagles,
golden retrievers, Doberman pinschers, Great Danes).13
� Group 1 dogs have one or more signs of hypothyroidism, most com-
monly including indications of decreased basal metabolic rate
(weight gain without historical increase in appetite, cold intolerance
or heat seeking, exercise intolerance, lethargy) and dermatological
changes (alopecia, seborrhea, dry coat and skin, hyperpigmentation,
myxedema, or recurrent pyoderma or otitis externa).
� Other systems that may be affected are cardiovascular (bradycardia)
and neurologic, with signs related to the peripheral nervoussystem
(i.e., facial nerve paralysis), vestibular and central nervous systems
(ataxia, seizures, obtundation), and polyneuropathy (weakness).7
Megaesophagus has been diagnosed in dogs with hypothyroidism,
but there is little evidence of a causative linkage.13
� Assess for consistent laboratory abnormalities such as hypercholes-
terolemia and hypertriglyceridemia (ideally on a fasted sample). A
mild nonregenerative anemia may also be present.
Next Steps
� Submit additional thyroid testing to document a subnormal fT4
and/or an elevated TSH concentration to confirm diagnosis.
� Approximately 20–40% of dogs with hypothyroidism have a low
TT4 and low fT4 but a normal TSH concentration.15,16 However,
this scenario could also indicate nonthyroidal illness, so additional
testing such as assessing for the presence of antithyroid autoantibo-
dies or a TSH response test can be run to help confirm diagnosis,
although these tests may be cost-prohibitive for some clients.24
� Initiate treatment with twice-daily levothyroxine supplementation
(ideally on an empty stomach to maximize absorption).
� Monitor therapy based on clinical improvement and serial TT4 test-
ing. Assess a TT4 level 4–6 hr post morning pill 4 wk after starting
medication or after dose adjustments until control is achieved, then
every 6–12 mo as indicated.
� Consider monitoring TSH level until normalized if it was elevated at
initial diagnosis (refer to treatment and monitoring section above).
GROUP 2: DOGS WITH NO CLINICAL SIGNS OF
HYPOTHYROIDISM AND A LOW TT4
Clinical Presentation
Group 2 dogs have no symptoms of hypothyroidism and a decreased
TT4 on routine laboratory screening.
Next Steps
� It is critical to consider the dog’s signalment, such as age and breed,
before proceeding with additional testing for hypothyroidism. Clini-
cally normal dogs of certain breeds such as greyhounds, Alaskan
sled dogs (particularly when racing), shar peis, salukis, and deer-
hounds are routinely reported to have TT4 concentrations that are
lower than established laboratory reference ranges. The guidelines
task force recommends using breed-specific reference ranges when
interpreting hormone levels in these breeds, especially if no clinical
signs are present.25
� Review current and previous medications. Drugs such as phenobarbi-
tal, clomipramine, toceranib phosphate, glucocorticoids, and sulfona-
mides are reported to lower TT4 and/or fT4 concentrations; TSH
may be increased or within the reference range, depending on the
mechanism of the effect on thyroid function. These changes are
reversible in most cases once the medications are discontinued.18,26,27
� Investigate for nonthyroidal illness if the dog is sick. Euthyroid sick
syndrome can decrease circulating thyroid hormone concentrations,
with preferential impact on TT4. In severe illness, fT4 is also
impacted. TSH may be subnormal or within the reference range.19
Ideally, further thyroid testing should be delayed until clinical illness
has resolved and the dog is clinically well.
� Review symptoms of hypothyroidism with owner and consider mea-
surement of fT4 and TSH levels if symptoms develop.
� Monitor for development of clinical signs.
4 JAAHA | 59:3 May/Jun 2023
GROUP 3: DOGS WITH CLINICAL SIGNS OF
HYPOTHYROIDISM AND A NORMAL TT4
Clinical Presentation
Group 3 dogs have a similar clinical presentation to Group 1 dogs,
but the TT4 does not confirm hypothyroidism.
Next Steps
� Investigate for other causes of clinical presentation by reviewing his-
tory with client and pursuing additional diagnostics.
� Perform an fT4ed with TSH and consider additional testing to rule
out thyroiditis, specifically assessing for the presence of antithyroid
autoantibodies. Dogs with thyroiditis can have antibodies that falsely
elevate TT4 levels because of cross-reactivity of the T4 autoantibo-
dies. Signs of hypothyroidism can develop slowly over time in some
of these dogs.3
� A TSH response test could be considered if the TT4 or fT4 concen-
trations are in the low-normal reference range and the patient lacks
circulating antithyroid antibodies.
� Dogs should be treated with supplementation if the diagnosis is
confirmed, and therapy is monitored as described for Group 1.
However, if the TT4 concentration was within reference range at
diagnosis owing to the presence of T4 autoantibodies, an fT4ed is
the preferred test to accurately monitor therapy.
Canine Hypercortisolism
(Cushing’s Syndrome)
Overview
Cushing’s syndrome (CS) refers to clinical signs associated with
excessive glucocorticoid exposure, including polyuria, polydipsia,
polyphagia, and panting. It can be caused by endogenous oversecre-
tion of cortisol or by exogenous administration of glucocorticoids
(iatrogenic etiology). Naturally occurring CS can be adrenocortico-
tropic hormone (ACTH) dependent (85%) or ACTH independent
(15%). The vast majority of cases of ACTH-dependent CS are caused
by a pituitary tumor (pituitary-dependent hypercortisolism, PDH),
and most cases of ACTH-independent CS are caused by adrenal
tumors (adrenal-dependent hypercortisolism, or ADH). Other
causes, including ectopic ACTH secretion and food-dependent
hypercortisolism, will not be discussed here.
Diagnostic Testing and Monitoring
All diagnostic tests for Cushing’s syndrome have limitations and can
yield false-positive results when performed in patients with concur-
rent nonadrenal illness or stress.28 Therefore, proper patient selection
is essential before testing and likely impacts diagnostic accuracy
more than which specific test is selected. Practitioners should only
test patients when clinical suspicion of CS is high (i.e., the presence
of two or more clinical or biochemical abnormalities suggesting CS).
Additionally, attempts should be made to stabilize or resolve any
known comorbidities (such as diabetes mellitus) before pursuing CS
testing when possible.29
The low-dose dexamethasone suppression test (LDDST) is the
preferred diagnostic test of the guidelines panel members. False posi-
tives can occur with stress or nonadrenal illness such as uncontrolled
diabetes.30,31 Results of the LDDST may also differentiate between
PDH and ADH.
Low-Dose Dexamethasone Suppression Test
Technique
1. Draw a serum sample for baseline cortisol measurement.
2. Administer 0.01 mg/kg of dexamethasone IV (if dexa-
methasone sodium phosphate is used, calculate dose
using a concentration of 3 mg/mL, instead of 4 mg/mL
as listed on the bottle).32
3. Collect serum samples for cortisol measurement at 4
and 8 hr.
Test results are interpreted as follows:
� Refer to laboratory’s diagnostic cutoffs for interpretation. The values
below are used as examples only.
� Assess the 8 hr result. Cortisol .1.4 mcg/dL is consistent with a
diagnosis of CS; continue with differentiation.
� If the 8 hr cortisol concentration is between 1.0 and 1.39 mcg/dL
but clinical suspicion for CS is high, consider performing an
ACTH stimulation test (ACTHST) or repeating the LDDST in
2–3 mo.
TABLE 2
Clinicopathologic Findings That Can Occur with Cushing’s
Syndrome
Increased alkaline phosphatase 
Hypercholesterolemia 
Mild hyperglycemia
Dilute urine (specific gravityconsiderations:
� Samples should be collected in a manner consistent with labora-
tory recommendations. Fasting is generally not required, but
excessive lipemia may affect results. If lipemia is present, seek lab-
oratory guidance for interpretation.
� Glucocorticoid withdrawal before testing should be 2 wk for
short-acting glucocorticoids, whereas up to 4 wk may be required
following use of longer-acting glucocorticoids (such as tri-
amcinolone).33–35
TheACTHST appears to be less impacted than the LDDSTby stress
and nonadrenal illness, particularly diabetes.29,30 The ACTHST should
also be considered if the LDDST does not support a diagnosis of hyper-
cortisolism but clinical suspicion remains high, to confirm iatrogenic CS,
and to monitor CS therapy. The testing procedure is detailed in the
ACTHStimulation Technique box, with results interpreted as follows:
1. Refer to laboratory’s diagnostic cutoffs for interpretation. Values
indicated here are used as examples only.
2. If the 1 hr post-ACTH cortisol exceeds 22 mcg/dL, this is consistent
with CS.
3. If the ACTHST returns with both the pre- and stimulated cortisol
in ranges that mimic hypoadrenocorticism, this is consistent with
iatrogenic CS, and additional investigation into glucocorticoid expo-
sure is warranted. This pattern may also be seen in dogs with ADH;
an LDDST should be performed if iatrogenic hypercortisolism is
excluded.
Relevant considerations for the ACTHST are as follows:
1. False-positive results can occur in dogs that are chronically or mod-
erately stressed or have nonadrenal illness but are less common
than with LDDST.30
2. This test lacks sensitivity in dogs with adrenal tumors, leading to
false-negative results in up to 41% of dogs with ADH.36 If the stim-
ulated cortisol concentration is below the diagnostic cutoff and clin-
ical suspicion of CS remains high, an LDDST should be performed.
3. See “Relevant Considerations” for LDDST, above.
The urine cortisol-to-creatinine ratio (UCCR) test is highly sen-
sitive but poorly specific, leading to a large number of false positives,
particularly in dogs with polyuric conditions. It is most appropriately
used to exclude hypercortisolism in patients with a low clinical suspi-
cion of CS, such as an asymptomatic dog with an alkaline phospha-
tase (ALP) elevation. To minimize the risk of false-positive results,
urine samples are best collected in a nonstressed, home environ-
ment.37 A low value (based on the laboratory’s diagnostic cutoff)
almost always rules out the disease.
Therapy
Adrenalectomy is the preferred therapy for ADH. However, clients
may decline this option because of cost, potential complications, and
comorbidities. Mitotane is an adrenocorticolytic drug that was previ-
ously the primary treatment option for PDH and is still preferred by
some clinicians. Please see Behrend for more information.38 Trilos-
tane is FDA approved for treatment of PDH and ADH. Although
labeled to be administered once daily, there are several peer-reviewed
references that have found that twice-daily use may be prefera-
ble.39–41 The FDA-approved dose is 2.2–6.7 mg/kg/day, but it has
been commonly used at lower doses such as 2–3 mg/kg/day. Several
members of the guidelines task force use a starting dosage of
�1 mg/kg twice per day, dependent on the FDA-approved commer-
cially available capsule sizes.
Monitoring requires close attention to clinical signs and cortisol
testing. There are many published monitoring and testing protocols;
there is no universal consensus on one protocol.42 The ACTHST has
historically been used for monitoring mitotane and trilostane ther-
apy, but more recent research shows that ACTH-stimulated cortisol
has poor correlation with clinical signs in dogs treated with trilos-
tane.43,44 As the ACTHST is the only definitive diagnostic test for
diagnosis of hypoadrenocorticism, the primary role for its use in
monitoring treatment of naturally occurring CS is to rule out oversup-
pression of cortisol production. Because CS is a highly variable dis-
ease, clinician judgment and discretion are important in deciding on a
specific monitoring protocol. There is consensus among the guidelines
TABLE 3
Clinical Signs Associated with Naturally Occurring Cushing’s
Syndrome
Polyuria (± worsened incontinence, urinary accidents, 
and/or nocturia) 
Polydipsia 
Pot-bellied appearance 
Polyphagia 
Excessive panting 
Dermatopathy 
Muscle weakness or wasting
6 JAAHA | 59:3 May/Jun 2023
panel that the protocols and testing guidance described below have
been effective. Initial response is assessed at 2 wk, then 1 mo later,
and then every 3–6 mo. Clinical signs are the primary indicator of
whether the patient is controlled or needs a dose adjustment.
Measurement of cortisol concentrations (before pill or following
ACTHST) is recommended to help determine whether it is safe to con-
tinue with the current dose or to adjust the dose. Pre-pill cortisol testing
involves obtaining a sample for cortisol measurement before the morn-
ing pill. The ACTHST should be done 3–5 hr after trilostane adminis-
tration, with a lower dose of synthetic ACTH (1 mcg/kg IV) being
acceptable for monitoring.45 Timing of when the ACTHST is started
following trilostane administration should be consistent between visits.
The primary purpose of the first recheck at 2 wk following initia-
tion of trilostane treatment is to ensure cortisol is not becoming too
low. Therefore, at the first 2 wk recheck following trilostane initiation,
the guidelines authors do not usually recommend increasing the dose
but may decrease the dose. After the first month of treatment, neces-
sary dose increases are typically by 25–50% based on commercially
available capsule sizes. Owners should not give trilostane if the dog is
not feeling well. The guidelines task force does not routinely recom-
mend, but recognizes, that patients are sometimes on unequal doses
twice daily. Cortisol monitoring should always be performed follow-
ing the higher dose. For example, if a patient is receiving 40 mg and
30 mg, an ACTHST should be performed after the 40 mg dose.
TABLE 4
Summary of Categorical Approach to Diagnosing Suspected Canine Hypercortisolism (Cushing’s Syndrome)
2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines—Final
JAAHA.ORG 7
Clinical Tips
• A follow-up client questionnaire (available at aaha.org/
endocrine-disease under the Resource tab) is a useful
instrument for the client to complete at presentation of
the patient. Answers to this questionnaire and follow-up
questions about clinical signs are the primary determi-
nants of whether the patient needs a dose adjustment.
• Cortisol measurements help determine whether the cur-
rent dose is appropriate or if dose adjustment is needed
for a patient.
Categorical Approach to Diagnosis Based on
Clinical Presentation
In the past, patients have been diagnosed with CS based on classic clin-
ical signs (polyuria, polydipsia, polyphagia, panting, and dermatologic
abnormalities), clinicopathologic abnormalities (increased ALP and
cholesterol, stress leukogram, thrombocytosis, urine specific gravity
,1.020, and proteinuria), and definitive diagnostics (LDDST or
ACTHST). However, as awareness of CS has increased, clinical suspi-
cion has also increased in patients with more ambiguous presentations
that may lack some of the classic clinical signs or clinicopathologic
abnormalities. The purpose of the information in this section of the
guidelines is to help the practitioner navigate the diagnostic pathway in
patients with various presentations.
GROUP 1: CLINICAL SIGNS AND CLINICOPATHOLOGIC
FINDINGS CONSISTENT WITH CUSHING’S SYNDROME
Clinical presentation
These are the dogs with classic signs and clinicopathologic abnormal-
ities expected with CS (Tables 2 and 3).
Next Steps
� Minimum database should include complete blood count, serum
biochemistry, and urinalysis. Consider assessingblood pressure,
urine culture, and urine protein:creatinine ratio.
� Specific endocrine testing should be performed. The guidelines panel
recommends an LDDST as a routine first step. If the LDDST con-
firms CS, consider differentiation between PDH and ADH (if not
differentiated by the LDDST) and appropriate therapy.
� Differentiation between PDH and ADH is helpful because it helps
direct therapeutic options and provides the owner with prognostic
information. However, if the owner has no intention of pursuing
adrenalectomy if an adrenal tumor is identified, patients can be trea-
ted with trilostane without knowing whether the dog has PDH
or ADH.
� Diagnostics that help differentiate PDH from ADH include LDDST,
abdominal ultrasound, and endogenous ACTH concentration.
� Computed tomography of the head may be performed in dogs with
PDH if the dog has signs compatible with a macroadenoma or if the
owner would pursue radiation therapy or hypophysectomy.
� In patients with ADH, abdominal computed tomography is usually
pursued before adrenalectomy.
� If the LDDST is not confirmatory, perform an ACTHST. If the
ACTHST is confirmatory, consider differentiation and therapy. If
the ACTHST is not confirmatory, consider referral to a specialist.
� Note that endocrine diagnostics should not be performed within
2 wk of administration of short-acting glucocorticoids (oral,
otic, or ophthalmic) or within 4 wk of receiving long-acting
glucocorticoids.33–35
GROUP 2: DOGS WITH NO CLINICAL SIGNS, BUT WITH
CLINICOPATHOLOGIC ABNORMALITIES SUGGESTIVE OF
CUSHING’S SYNDROME
Clinical presentation
Group 2 dogs are those for whom the owners report no clinical signs
consistent with CS but have one or more compatible clinicopatho-
logic abnormalities (Table 2).
Next Steps
� The first step in managing these patients is to thoroughly probe the
patient’s history, with specific questions about water intake, urina-
tion habits, worsened incontinence, or nocturia. Potential adminis-
tration of glucocorticoids, including ophthalmic or otic preparations,
should also be ruled out.
� Repeat testing to confirm persistence of previous abnormalities.
� If no clinical signs of CS are identified, consider alternative differen-
tials for clinicopathologic abnormalities, and pursue appropriate
diagnostics. For example, for an increased ALP concentration,
abdominal imaging may be performed.
� Specific endocrine testing is not necessary unless or until clinical
signs of CS are present.
� A UCCR test may be considered if the veterinarian or client is highly
motivated to rule out the diagnosis of CS. Note that the UCCR test is a
very sensitive but nonspecific test. Although a negative result makes CS
very unlikely, a positive result does not confirm the presence of CS.
GROUP 3: DOGS WITH CLINICAL SIGNS SUGGESTIVE
OF CUSHING’S SYNDROME WITHOUT CLINICOPATHO-
LOGIC ABNORMALITIES
Clinical presentation
Clinical signs in Group 3 dogs may include polyuria, polydipsia,
polyphagia, excessive panting, and dermatopathy (Table 3).
Next Steps
� Carefully question the owner to rule out administration of glucocor-
ticoids that could cause CS.
� If clinical suspicion of CS is low, monitor the patient’s progression
or change in clinical signs. A UCCR test can be considered to rule
out CS.
8 JAAHA | 59:3 May/Jun 2023
� If clinical suspicion is high, specific endocrine testing is recom-
mended. In patients without significant comorbidities (such as dia-
betes mellitus), an LDDST is recommended.
� If CS is confirmed, consider differentiation (see GROUP 1). If CS is
not confirmed, consider other differential diagnoses for the specific
clinical signs.
� If CS is still strongly suspected, ACTHST and/or consultation with a
specialist may be pursued.
GROUP 4: SICK PATIENTS PRESENTING WITH SIGNS
AND/OR CLINICOPATHOLOGIC FINDINGS CONSISTENT
WITH CUSHING’S SYNDROME
Clinical presentation
Group 4 dogs are patients that may have CS but whose presenting
signs must be addressed before pursuing diagnostics for CS. Note
that hypercortisolism does not cause anorexia, vomiting, or diarrhea.
Patients in this category may include:
� Dogs in whom the presenting signs are due to a disease process that
is unrelated to CS (e.g., acute gastroenteritis)
� Dogs with presenting signs caused by a comorbidity associated with
CS (e.g., pulmonary thromboembolism, gall bladder mucocele, or
diabetic ketoacidosis)
� Dogs with signs of an enlarging macroadenoma (decreased appe-
tite, behavior change, or other neurologic signs). In these cases,
the macroadenoma is causing the presenting signs; hypercortiso-
lism is not.
Next Steps
� Address the presenting clinical signs and underlying cause of the
acute illness.
� Do not perform specific endocrine testing for CS until the acute ill-
ness is managed or controlled. Acute illness causes stress that can
lead to false-positive results, particularly with the LDDST. Addition-
ally, because CS is not causing the presenting clinical signs, diagnosis
and treatment of CS will not immediately ameliorate the presenting
clinical signs.
� If relevant, treatment of diabetes mellitus should not be delayed in
dogs with suspected CS.
� The guidelines task force recommends, if possible, waiting at least
2–4 wk after improvement of the acute illness to test for CS.
� If the acute or chronic illness is unlikely to resolve or improve with-
out addressing the possible underlying CS, consider consultation
with a specialist to discuss the need for and timing of specific endo-
crine testing.
Canine Hypoadrenocorticism
(Addison’s disease)
Overview
Hypoadrenocorticism (HA), or Addison’s disease, describes a
spectrum of conditions resulting in deficiencies of important adre-
nal hormones (i.e., cortisol and aldosterone). HA usually results
from direct adrenocortical injury (primarily autoimmune disease)
although the rapid withdrawal of adrenal suppressive medications
(steroids), pituitary surgery, or cancer sporadically result in
ACTH deficiency. The variable clinical signs correspond to a loss
of the vital functions of cortisol in maintaining metabolism,
immunity, and gastrointestinal health and of aldosterone in main-
taining sodium and volume status. Recent studies suggest up to
25–30% of patients with HA have normal electrolytes (i.e.,
“atypical” HA).46–48
The clinical signs of HA can occur in dogs of any age or breed.
Most dogs are diagnosed in middle age, with a female predisposition
inconsistently reported. Commonly affected breeds include the stan-
dard poodle, Portuguese water dog, and Great Dane. Often, sudden
signs of volume depletion (shock) predominate in “typical” HA (cor-
tisol deficiency with aldosterone deficiency), although the atypical
form (clinical signs reflecting cortisol deficiency without electrolyte
TABLE 5
Diseases with a Similar Clinical Presentation to
Hypoadrenocorticism
Conditions with similar clinical presentation to classic HA
• Acute kidney injury
• Severe gastrointestinal disease
Diseases with a similar clinical presentation to atypical HA
• Severe gastrointestinal disease
• Hepatic dysfunction
HA, hypoadrenocorticism.
TABLE 6
Conditions That Biochemically Resemble Hypoadrenocorticism
(Pseudo-Addisonian Conditions)
Whipworms
Third spacing of fluids
Chronic gastrointestinal disease
Renal failure
Hepatic failure
Reperfusion injury
Acidosis
Artifact (thrombocytosis, hemolysis) 
2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines—Final
JAAHA.ORG 9
derangements) is more often chronic. Atypical HA is characterized
by vomiting, lethargy, anorexia, and diarrhea; hypoalbuminemia
and/or hypocholesterolemia are common laboratory findings.49
The presence of a lymphopenia makes cortisol deficiency extremely
unlikely.50
Diagnostic Testing and Monitoring
The diagnosis relies on confirming cortisol deficiency by means of
an ACTHST. A sodium-to-potassium ratio ,27 is suggestive, al-
though sodium and/or potassium concentrations are within the ref-
erencerange in nearly one in four cases of HA, and many other
disorders can impact the sodium-to-potassium ratio.49,51 Aldosterone
measurement is available through multiple laboratories and can be
used to further determine adrenal function if appropriate.52
The finding of a baseline or “resting” serum cortisol .2 mcg/dL
rules out HA with nearly 100% confidence, assuming that the patient
has not received exogenous glucocorticoids known to cross-react
with the cortisol assay (such as prednisone).53 However, most dogs
with a baseline cortisol ,2 mcg/dL do not in fact have hypoadreno-
corticism, so this finding is not sufficient to establish the diagnosis.
The diagnosis is confirmed by a post-ACTH stimulation cortisol value
,2 mcg/dL or below the laboratory-specific diagnostic cutoffs (see
box, ACTH Stimulation Technique). Reference ranges derived from
healthy pets are not the same as diagnostic cutoffs, which are devel-
oped by sampling dogs with HA. Measurement of endogenous
ACTH, specifically the cortisol-to-endogenous ACTH ratio, or a
UCCR are promising sensitive and specific tests for dogs with pri-
mary adrenocortical injury, although this test is not yet routinely
performed.54–58
Therapy
For cortisol deficiency, a small daily dose of glucocorticoids is recom-
mended. Many dogs require doses ,0.1 mg/kg/day of prednisone or
prednisolone, and 0.25 mg/kg/day should be enough to manage all clin-
ically stable dogs with HA long term. Other glucocorticoids are accept-
able, and the dose should be calculated on a prednisone-equivalent
basis. The daily dose should be doubled or tripled before known stress-
ful events.
Dose should be further adjusted based on clinical signs and
side effects. Dose should be increased when a dog shows clinical
signs of Addison’s disease, such as anorexia, lethargy, vomiting,
diarrhea, hematochezia, and melena. Dose should be decreased
when the dog has side effects of glucocorticoid administration
including polyuria/polydipsia, polyphagia, panting, muscle wast-
ing, elevated ALP, or hair loss.
Patients with hyperkalemia and/or hyponatremia require min-
eralocorticoid supplementation. The labeled dose of desoxycorticos-
terone pivalate (DOCP) is 2.2 mg/kg given intramuscularly or sub-
cutaneously, but research has demonstrated efficacy with lower
doses.59,60 Starting doses of 1.1–1.5 mg/kg may be appropriate in
most cases.61,62
The dose and the dosing interval are determined by electrolyte
monitoring. Check electrolyte levels 10–14 days after injection and
again 25 days after injection. If hyperkalemia or hyponatremia are
persistent, the dose is typically increased. If electrolytes are normal,
the dose may be gradually decreased with monitoring. If the dose is
already low, extending the dosing interval to 28–30 days is reason-
able.60 If DOCP cannot be used, consideration can be given to using
fludrocortisone.
TABLE 7
Laboratory Changes That Can Occur with Hypoadrenocorticism
10 JAAHA | 59:3 May/Jun 2023
ACTH Stimulation Technique
1. Collect a baseline serum cortisol sample. The patient
may need to be fasted to avoid lipemia.
2. Inject cosyntropin (5 mcg/kg intramuscularly or IV up
to 250 mcg per dog) and collect a second serum sample
1 hr later.
a. A 1 mcg/kg dose of cosyntropin has been shown
equivalent to a 5 mcg/kg dose of cosyntropin for
most dogs suspected of HA.63
b. A 1 mcg/kg dose of cosyntropin has been shown appro-
priate for monitoring of dogs with Cushing’s syndrome
being treated with trilostane or mitotane but is not reliable
for the diagnosis of Cushing’s syndrome.45
c. The absorption of compounded ACTH-depot (“gel”)
may be delayed from the intramuscular space. Thus,
samples for cortisol should be collected at both 1
and 2 hr after injection.
3. The cost of the cosyntropin can be decreased by using
lower doses when appropriate and by freezing the
reconstituted product in small aliquots.64
a. Using an aseptic technique, reconstitute the ACTH
solution for injection as instructed on the package
(1 mL NaCl for a 250 mcg/mL solution).
b. With a tuberculin syringe, draw up 0.1–0.2 mL ali-
quots. Draw up an additional 0.1 mL of air to pro-
vide space for expansion during freezing. Store at
20�C for up to 6 mo.
c. At the time of use, thaw one or more syringes in the
palm of a gloved hand. The solution will quickly liq-
uefy. Expel the small air bubble from the hub before
use and double-check drug volume.
d. Once thawed, use or discard the solution. Do not
refreeze.
Clinical Tips
• Clients as well as veterinary health care professionals
can learn to administer subcutaneous injections. Once a
stable dose and dosing interval are achieved, monthly
DOCP injections may be administered by someone
other than the veterinarian.
• Other health care team members may serve as the pri-
mary client educators regarding symptoms of illness
and side effects.
• Routine biannual health care visits are still encouraged.
Categorical Approach to Diagnosis Based on Clinical
Presentation
Although some dogs with hypoadrenocorticism present with typical
physical examination and laboratory abnormalities, making diagnosis
relatively straightforward, other cases may have a vague or atypical
presentation. The clinical signs or laboratory findings associated with
hypoadrenocorticism can mimic several other diseases, making diag-
nosis challenging. The guidelines panel has organized clinical presen-
tations into four groups to aid in diagnosis.
GROUP 1: CLASSIC CLINICAL DISEASE
Clinical Presentation
Group 1 dogs present with chronic or episodic clinical signs and lab-
oratory abnormalities consistent with hypoadrenocorticism.
Next Steps
If suspicion for disease is high, an ACTHST should be performed to
confirm diagnosis. If suspicion for disease is low, a resting cortisol
could be performed. If the resting cortisol is ,2 mcg/dL, an
ACTHST should be performed to diagnose hypoadrenocorticism. If
the resting cortisol is .2 mcg/dL, other differentials for these clinical
and laboratory abnormalities should be pursued.
Once the diagnosis of hypoadrenocorticism is confirmed,
appropriate treatment(s) and monitoring should be instituted. For
patients with classic clinical disease, treatment generally consists of
both mineralocorticoid and glucocorticoid supplementation.
GROUP 2: NO CLINICAL SIGNS, BUT WITH CLASSIC
LABORATORY ABNORMALITIES
Clinical Presentation
Group 2 dogs present without clinical signs of disease and have labo-
ratory derangements on routine laboratory work, which include
hyperkalemia and/or hyponatremia. Additional laboratory abnormal-
ities may be present (Table 7).
Next Steps
In these cases, the owner should be requestioned as to the presence of
associated clinical signs including questions related to gastrointestinal
health (appetite and stool), energy, and water intake. If upon deeper
analysis there are still no clinical signs of hypoadrenocorticism, other
causes of laboratory changes such as spurious causes should be ruled
out (Table 6). If the blood sample was run on serum, consider reeva-
luation of plasma because serum potassium levels can be artificially
high due to potassium release from platelets during clot formation.65 If
no clinical signs are present and spurious causes have been excluded,
monitor clinical signs and repeat the laboratory testing as indicated.
If laboratory abnormalities are persistent or progressive, or
upon deeper analysis clinical signs are present, either a resting
2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines—Final
JAAHA.ORG 11
cortisol should be considered to exclude this disease or an ACTH
stimulation test (ACTHST) could be performed.52 If a resting cortisol
test is chosen and results are ,2 mcg/dL, an ACTHST should be
performed to confirm the diagnosis.
GROUP 3: ADDISONIAN CRISIS
Clinical Presentation
Group 3 dogs present in hypovolemic shock with or without historic
episodic signs consistent with hypoadrenocorticism.This is the most
serious and life-threatening manifestation of hypoadrenocorticism
and typically presents as hypovolemic shock accompanied by severe
hyperkalemia and hyponatremia. Other laboratory abnormalities
may be seen (Table 7).
Next Steps
Immediate stabilization should be implemented, with IV fluids being
the cornerstone of therapy. Treatment should target correcting hypo-
volemia and hypotension. Specific therapy to correct hyperkalemia,
hypoglycemia, and acidosis may be required. Gastrointestinal support
including early enteral nutrition should be implemented as needed.
Once stable, these patients may need to be transferred to a facil-
ity that provides 24 hr care to provide continued support. Frequent
monitoring of electrolytes is required. The guidelines task force
recommends daily packed cell volume monitoring as these patients
can become severely anemic following rehydration.66
Once stable, perform a baseline cortisol test to rule out this
diagnosis, or, if suspicion for disease is high, perform an ACTHST to
TABLE 8
Summary of Categorical Approach to Diagnosing Suspected Canine Hypoadrenocorticism
12 JAAHA | 59:3 May/Jun 2023
confirm diagnosis. In some cases, administering a single dose of a
steroid before testing is required for stabilization. Dexamethasone
(0.1 mg/kg IV) is the steroid of choice because it does not interfere
with the cortisol assay.66 Consider aldosterone measurement. Miner-
alocorticoids can be started once the patient is stable, there is a con-
firmed diagnosis, and sodium is .130 mEq/dL.
GROUP 4: CLINICAL SIGNSWITHNONSPECIFIC LABORATORY
ABNORMALITIES (ATYPICAL PRESENTATION)
Clinical Presentation
Group 4 dogs present with chronic or episodic clinical signs without
the characteristic findings associated with classic hypoadrenocorti-
cism. Because signs of canine hypoadrenocorticism can mimic many
other diseases, patients may present with episodic clinical signs that
could be consistent with this disease without the hallmark laboratory
findings of hyperkalemia or hyponatremia (Table 6).
Next Steps
When signalment and clinical signs are consistent with hypoadreno-
corticism (e.g., episodic gastrointestinal signs after periods of stress,
polyuria/polydipsia) or if there are other suggestive laboratory find-
ings (Table 7), a resting cortisol should be performed. If the resting
cortisol is ,2 mcg/dL, an ACTHST should be performed. If the rest-
ing cortisol is .2 mcg/dL, other differentials should be considered.
If hypoadrenocorticism is diagnosed, consider testing for aldosterone
deficiency as many of these patients have hypoaldosteronism, even
with normal electrolytes.51 Appropriate treatment and monitoring
should be instituted based on diagnosis.
Feline Hyperthyroidism
Overview
The management of FHT has been covered extensively in other pub-
lications, notably the 2016 AAFP Guidelines for the Management of
Feline Hyperthyroidism.2 Much of the information in the 2016 AAFP
guidelines remains applicable today. This discussion of FHT will
serve to highlight certain key points and present recent findings
related to the disease.
FHT is an extremely common endocrinopathy in cats, resulting
from excessive circulating levels of T4 and T3. These excess hormone
levels are most often caused by benign adenomatous hyperplasia of
one or both thyroid glands and create a state of increased metabo-
lism. Thyroid carcinoma is a rare FHT etiology, present in fewer
than 3% of cats at the time of initial diagnosis.67 Although FHT is
typically diagnosed in cats older than 10 yr, elevated T4 levels in
younger cats may be found more often as annual blood screening
becomes more commonplace. It is important to note that T4 levels
naturally decrease with age. A senior or geriatric cat with high normal
T4 values according to the reference laboratory may actually be
hyperthyroid. Following trends on annual screenings should reveal
T4 levels either static or dropping. Elevation over time with develop-
ment of clinical signs warrants further confirmation testing, even if
the T4 level is technically within the laboratory’s normal range.
Diagnosis and Monitoring
The classic presentation of FHT (also known as Group 1 in the 2016
AAFP guidelines and in Table 8) is a cat that is losing weight, eating
voraciously, and hyperactive. Many cats, however, do not have these
classic signs and can be assigned to one of the other five diagnostic
groups. Cats with elevated T4 levels on basic blood screens may be
minimally symptomatic or asymptomatic. Regardless of the cat’s
clinical presentation, a repeatedly elevated T4 level requires treat-
ment to prevent progression of the disease and subsequent secondary
organ damage.
Concurrent disease may cause the serum T4 level to be lower
than expected in a cat suspected to be hyperthyroid. In these cases, a
fT4 will be helpful to confirm the diagnosis. For cats that fall into
Groups 4 or 6 that may be considered early or subclinically hyperthy-
roid, there may be some benefit to measuring TSH levels before
deciding on treatment options. Cats with detectable serum TSH con-
centrations ($0.03ng/mL) are at much higher risk for development of
131I-induced hypothyroidism.68 A commercially available feline TSH
test was recently released; however, the canine TSH test is a reasonable
alternative.69,70 A measurable TSH level may make a cat more suscepti-
ble to hypothyroidism following radioactive iodine treatment. Waiting
until TSH declines to an unmeasurable level may be beneficial.68,70
TSH levels are not sensitive for initial diagnosis of hyperthyroidism
and must be used in conjunction with elevated T4 or fT4 levels.70
Therapy
Left untreated, FHT will eventually be fatal. Hyperthyroidism affects
multiple organ systems. Until FHT is corrected, management and
assessment of comorbidities cannot be accurately assessed. Options
for treatment include radioactive iodine, oral antithyroid medication,
surgical removal of the adenomatous thyroid gland, and an iodine-
deficient therapeutic diet. The treatment of choice is radioactive
iodine (131I), which will provide a cure in more than 95% of cases.
Radioactive iodine avoids anesthesia, requires no ongoing medica-
tion administration, and does not require the cat to have a restrictive
diet. Radioactive iodine may be used as an initial treatment for stable
hyperthyroid cats, even in the presence of some concurrent diseases.
Cats with elevated N-terminal pro-B-type natriuretic peptide levels
and mild heart disease will likely benefit from having the hyperthy-
roid state corrected. Cats with mild renal changes (IRIS stage 1) can
2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines—Final
JAAHA.ORG 13
also be treated with 131I without a therapeutic medication trial first.2
Note that cats with normal renal and symmetric dimethylarginine
values may develop abnormalities after the hyperthyroidism is cor-
rected, and a normal symmetric dimethylarginine cannot be used to
predict renal function after hyperthyroid resolution.71 Iatrogenic
hypothyroidism is a risk of 131I, so ensuring the TSH concentration
is nondetectable before referral may be ideal.70
Important Note
• The AAHA guidelines task force recommends for AAFP
groups 4 and 6, the practitioner should consider check-
ing TSH prior to 131I treatment and postponing if mea-
surable (.0.03 ng/mL) to help avoid creating iatrogenic
hypothyroidism.70
Unfortunately, radioactive iodine treatment may not be avail-
able to all practitioners. Thyroidectomy may be curative, but it
includes the risk of anesthetizing a cat with potential cardiac com-
promise. The parathyroid glands are at risk of being damaged dur-
ing thyroidectomy even by skilled surgeons. Infrequently, there may
be ectopic thyroid tissue that is not easily surgically removed that
will continue to be overactive. Before surgical intervention, the cat
should be medically stabilized.
An iodine-deficientdiet is commercially available by prescrip-
tion and is effective for many cats in controlling hyperthyroidism.
Depending on the degree of initial elevation of the T4 level, some
cats may take several months to become regulated.72 For the thera-
peutic diet to be effective, cats must not be allowed access to any
other food, including other pets’ foods and human food, as well as
items that they may hunt and eat outdoors. In some cats, the T4 level
TABLE 9
Summary of Categorical Approach to Diagnosing Suspected Feline Hyperthyroidism�
14 JAAHA | 59:3 May/Jun 2023
will fail to normalize even after prolonged periods of exclusively
feeding the restrictive diet. It has been shown that feeding the
iodine-deficient diet to nonhyperthyroid cats in the household is not
harmful if it is not possible for owners to feed separate diets in multi-
cat homes.72
Medical management with methimazole is a common and
effective way of controlling hyperthyroidism. To minimize potential
adverse effects, methimazole should be started at a low dose and
titrated up to the dose needed to maintain T4 levels between 1.0 and
2.5 mcg/dL. Dosing of 1.25–2.5 mg every 24 hr for the first week
of treatment, increasing to 2.5–5 mg every 12–24 hr, will help mini-
mize side effects, although adverse effects including vomiting, bone
marrow dyscrasias, and skin excoriations can occur up to several
months after initiating therapy. Gastrointestinal side effects may
be mitigated by using a transdermal preparation of methimazole;
however, all other adverse drug effects require discontinuation
and selection of a different treatment method. Methimazole doses
will need to be adjusted over time because the drug does not
affect the growth of the adenomatous hyperplasia. Avoidance
of hypothyroidism is imperative and requires periodic veterinary
monitoring.
Clinical Tips
• For many practitioners, it has become commonplace for
pet owners to do their own research when a diagnosis
is made and subsequently propose alternative therapies.
For cats with FHT, there is no effective homeopathic
remedy despite the availability of products claiming to
be effective.73 Clients should be advised to pursue tradi-
tional treatments for this disease.
• If initial regulation is with methimazole, T4 monitoring
should occur every 2–4 wk until the goal levels are
reached. Complete blood count, chemistry profiles, and
urinalysis will provide information on potential bone
marrow dyscrasias, development or progression of azo-
temia, resolution of any liver enzyme changes, and any
other issues that may have been concealed by the hyper-
thyroid state.
• Blood samples for T4 measurement may be taken at any
time during the day after methimazole administration.
There is no need to schedule sampling for a specific time
after medication administration.68
• Once the patient has been regulated, a physical exami-
nation and minimum database should be performed at
least every 6 mo and more frequently if there are signif-
icant comorbidities.
Categorical Approach to Diagnosis Based on Clinical
Presentation�
GROUP 1: CLASSIC CLINICAL DISEASE
Clinical Presentation
Cats with uncomplicated clinical hyperthyroidism and elevated T4.
These are cats with one or more clinical signs consistent with FHT
that have an elevated T4 and no identifiable concurrent disease. T4 is
above the laboratory reference interval in FHT cases.
Next Steps
The AAFP Guidelines Panel recommends that reference laboratory
testing be utilized for diagnosis and monitoring of FHT so that pre-
cise serum hormone levels can be followed throughout treatment
and to avoid quality control discrepancies. Ideally, for purposes of
consistency, monitoring should be performed at the same reference
laboratory. If in-clinic testing is performed for geriatric screening
and significant changes are noted in thyroid hormone levels, obtain
confirmatory testing at a reference laboratory.
Complete blood count (CBC) findings are generally unremark-
able, although macrocytosis may be present. Cats with marked ane-
mia may suffer from a comorbidity and further work-up should be
performed. Serum chemistry findings often include elevated serum
alanine transferase (ALT) or alkaline phosphatase. Serum ALT levels
can be markedly elevated.
If liver enzymes do not normalize after successful treatment for
FHT, further diagnostic work-up is warranted. Azotemia may sug-
gest dehydration or underlying renal failure. Urinalysis results are
variable, although the urine specific gravity may be less than 1.030
due to primary polydipsia or inability to concentrate the urine due
to hyperthyroidism.
Management of Group 1 cats consists of treatment for their
hyperthyroid disease.
GROUP 2: POSSIBLE FHT WITH PROBABLE
NON-THYROIDAL DISEASE
Clinical Presentation
Cats with clinical hyperthyroidism and normal T4. Cats in this cate-
gory have clinical signs suggestive of FHT along with T4 within the
laboratory reference interval.
Next Steps
The AAFP Guidelines Panel recommends the following approaches
for Group 2 cats:
� Further testing for FHT should consist of T4 and fT4 assays mea-
sured 2–4 weeks after the initial blood screening. A T4 value in the
upper half of the reference interval combined with an elevated fT4
supports a diagnosis of hyperthyroidism.
2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines—Final
JAAHA.ORG 15
� If the T4 and fT4 are both within the reference interval, the cat
should be evaluated for non-thyroidal disease.
� If no concurrent illness is found and FHT is still suspected, further
testing is warranted, including triiodothyronine (T3) suppression
testing, serum TSH concentration in conjunction with T4 and
fT4ed, or thyroid scintigraphy.
NOTE: Common conditions with signs similar to FHT: Certain classic
signs of hyperthyroidism (polydipsia, polyuria, weight loss in the face
of a good appetite) have similarities with the following morbidities
that are plausible differential diagnoses:
� Diabetes mellitus
� Gastrointestinal malabsorption, maldigestion
� Gastrointestinal neoplasia, especially lymphosarcoma
GROUP 3: ENLARGED THYROID GLAND WITHOUT
CLINICAL FHT
Clinical Presentation
Cats without clinical hyperthyroidism, T4 within the reference inter-
val, but with enlarged thyroid gland(s).
Next Steps
Monitor clinical signs in these cats and repeat a serum T4 assay in
6 months.
GROUP 4: SUBCLINICAL FHT
Clinical Presentation
Cats without overt clinical hyperthyroidism but with an elevated T4
and with some physical exam findings suggestive of hyperthyroidism.
Next Steps
Repeat the T4 test in 1–2 weeks. If serum T4 is still elevated, treat
the cat for FHT. While no data exist for the best way to manage
Group 4 cats, the consensus of the Panel is to treat these cats for
hyperthyroidism. If a repeat T4 is normal, then re-evaluate the
patient in 6 months with a complete physical exam and a T4 assay.
GROUP 5: CLINICAL FHT WITH CONFIRMED
NON-THYROIDAL DISEASE
Clinical Presentation
Cats with clinical hyperthyroidism confirmed by elevated T4, and
one or more concurrent diseases.
Next Steps
Hyperthyroid cats are commonly middle-aged or older and often
have concurrent diseases. But because FHT is a serious disease that
can result in rapid deterioration of the patient, the Panel recom-
mends the treatment of all diagnosed cats, including those animals
with comorbidities. Appropriate monitoring and careful manage-
ment of concurrent diseases will optimize the patient’s health.
Common comorbidities associated with FHT:
� Thyrotoxic heart disease
� Hypertension
� Retinopathy
� CKD
� Gastrointestinal disease, malabsorption, cobalamin deficiency
� Insulin resistance
GROUP 6: CLINICALLY NORMAL
Clinical Presentation
Cats with no clinical signs of hyperthyroidism and no palpable thy-
roid nodule but with an elevated T4 on screening lab test.
Next Steps
Because falsely elevated T4 values may occur, repeat the T4 test prefera-bly using radioimmunoassay or chemiluminescent enzyme assay.74,75 If
the T4 is now normal, monitor the cat and retest T4 every 6 months,
or sooner if clinical signs develop. If the T4 is elevated, treat for FHT.
*Carney HC, Ward CR, Bailey SJ, et al. 2016 AAFP Guide-
lines for the Management of Feline Hyperthyroidism. J Feline
Med Surg. 2016;18(5):400-416, copyright © 2016 by SAGE Publi-
cations. Reprinted by Permission of SAGE Publications. Access
the AAFP Guidelines for Management of Feline Hyperthyroidism
and additional resources at catvets.com/hyperthyroidism.
Less Common Feline Endocrinopathies
Three feline endocrinopathies are encountered in clinical practice
with a lesser frequency than the other feline diseases discussed in
these guidelines: feline hyperaldosteronism, feline hypothyroidism,
and feline hyperadrenocorticism. This section provides general over-
views of these less prevalent but still important endocrinologic dis-
eases of cats.
Feline Hyperaldosteronism
The adrenal gland is the primary producer of the hormone aldoste-
rone, which is responsible in part for sodium and potassium homeo-
stasis. Feline primary hyperaldosteronism (PHA) is most commonly
caused by a unilateral adrenocortical adenoma, with malignant ade-
nocarcinomas reported less commonly.76
Cats with PHA are typically middle-aged to older cats. Present-
ing signs are typical of increased potassium loss/hypokalemia and
retained sodium. Hypokalemia, usually less than 3 mEq/L, will lead
to progressive muscle weakness. The owner may notice reluctance to
jump, abnormal gait (plantigrade stance), lethargy, or cervical ven-
troflexion. Because the cats are considered mature to senior, owners
often perceive clinical signs to be normal aging changes. Sudden
blindness due to retinal detachment is a consequence of persistent
systemic hypertension (SHT) and may or may not be noticed by the
16 JAAHA | 59:3 May/Jun 2023
owner. Hypertension before this catastrophic stage may cause non-
specific changes in behavior such as lethargy, hiding, and irritability.
Physical examination findings in cats with PHA may be related
to hypokalemia, systemic hypertension, or both. Muscle weakness
and atrophy may be present. Chronic kidney disease (CKD) is a fre-
quent comorbidity and can exacerbate the clinical impact of PHA.
Minimum database and Doppler blood pressure measurement
should be performed on cats with suspected PHA. Diagnostic imag-
ing with abdominal ultrasound (or cross-sectional imaging) may
reveal an adrenal mass. Ultrasound evaluation may reveal a unilateral
adrenal mass, up to 5 cm in diameter, but in some cases the adrenal
glands may appear normal.77 Plasma aldosterone testing is currently
the most readily available and reliable laboratory diagnostic tool, and
a single very high value may be confirmatory. More complex testing
may be needed in equivocal cases. Blood and urine changes consis-
tent with CKD may also be present and must be addressed.
Confirmation of unilateral or bilateral disease is important, as
it will influence treatment decisions.74 Surgical removal of the
affected adrenal gland is the treatment of choice for unilateral dis-
ease but may not always be an option.78 Affected cats need to be
stabilized medically before surgical intervention. Medical treatment
is focused on resolution of the hypokalemia and SHT. Potassium
supplementation, usually with potassium gluconate, is necessary,
and higher-than-standard doses may be required to restore normal
serum potassium concentrations. The aldosterone receptor blocker
spironolactone at 1–2 mg/kg given twice daily should be used to
help control hypokalemia. SHT must be corrected. Amlodipine
administered at 0.625–1.25 mg per cat per day is an effective and
affordable calcium channel blocker that is frequently used for SHT.
Feline Hypothyroidism
Although naturally occurring hypothyroidism in cats occurs rarely
compared with its incidence in dogs,79 it is occasionally reported in
this species. A single low T4 level should be interpreted in light of
the entire clinical picture because nonthyroidal illness can lead to
reductions of serum T4 levels. The magnitude of serum T4 suppres-
sion is proportionate to the severity of the underlying disease. Final
interpretation of thyroid function should be made when any non-
thyroidal illness is stabilized, as well as in relation to the cat’s clinical
presentation.
TABLE 10
Key Factors in Managing Feline Primary Hyperaldosteronism
Presentation
• Hypokalemia, frequently under 3 mEq/L, which may not respond well to supplementation.
• 
• Serum sodium concentrations are usually normal.
• Plasma aldosterone levels are elevated.
• Abdominal ultrasound or other imaging may show adrenal mass.
Therapeutic Recommendations
• Control hypertension.
• Supplement potassium.
• Use aldosterone receptor blocker.
• Consider surgical removal of the adrenal tumor.
Diagnostic Red Flags for Hyperaldosteronism
• Hypokalemia with no obvious cause, which may not respond well to supplementation.
• Hypophosphatemia +/- metabolic alkalosis despite azotemia.
• 
• Hypertension without concurrent cardiac or thyroid disease.
Take-Home Messages for Practice Team Members
• Signs of PHA can be subtle in the early stages.
• Blood pressure measurement should be a standard of care for adult cats at least annually, and any time a middle-age to 
older cat presents with nonspecific clinical signs.
PHA, primary hyperaldosteronism.
2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines—Final
JAAHA.ORG 17
Clinical signs of feline hypothyroidism are shown in Table 11.
Congenital hypothyroidism is usually identified in cats younger than
1 yr of age and most frequently in kittens younger than 8 mo.
Affected kittens are usually stocky, with shorter limbs and a broader-
than-usual head and neck. Lethargy, constipation, retained deciduous
teeth, abnormal hair coat, and thickened gingiva are common
findings.76
Diagnosis of hypothyroidism requires demonstration of a low
serum T4 (,0.8 mcg/dL) and elevated TSH concentrations. Demon-
stration of low serum fT4 levels may also suggest hypothyroidism. A
commercially available feline-specific TSH test was recently released;
however, the historically used canine TSH test will also be elevated in
cats with hypothyroidism.68 In contrast to hypothyroidism in dogs,
cats with naturally occurring hypothyroidism are more likely to be
azotemic.80 Figure 1 shows a diagnostic and treatment algorithm for
deciding if a low T4 indicates a patient has feline hypothyroidism.
Treatment of hypothyroidism in cats is straightforward and
similar to treatment in dogs. Levothyroxine sodium is recommended,
with an initial dose range of 0.05–0.1 mg daily. The dosage is
adjusted to target T4 levels between 1.0 and 3.0 mcg/dL; however,
clinical signs may persist for 2–3 mo before responding to treatment.
Adult-onset hypothyroidism, although rare, may in fact be
underdiagnosed in cats.81 Even if that proves to be true, it is still an
no
yes
no
no
no
no
yes
yes
yes
yes
Does this cat have concurrent disease?
Treat concurrent 
disease, then recheck 
T4 and TSH
Decrease dose by 25% 
and recheck in 2–4 weeks. 
Continue to reduce as 
needed until T4 is between 
1.0 and 2.5 mcg/dL
Is this a cat younger 
than 2 years with 
clinical signs?
Treat with levothyroxine
Recheck T4 in 2–4 weeks, 
if still low, check TSH and 
treat for hypothyroidism 
if elevated
Is this cat asymptomatic with no concurrent disease? 
If T4 is normal, 
not hypothyroid
If 4 months, if T4 is low 
and TSH is elevated, 
supplement with 
levothyroxine
Is this cat currently on 
methimazole for FHT?
Has this cat been treated 
for FHT with 131I or surgical 
removal of the thyroid?
noyes
Monitor 
laboratory values 
every 6 months 
and watch for 
clinical signs,